A phase 1b study of atezolizumab in combination with guadecitabine for the treatment of acute myeloid leukemia

Abstract

This phase 1 b study evaluated the safety, efficacy, and pharmacokinetics of atezolizumab in combination with guadecitabine in patients with relapsed/refractory (R/R) or first-line acute myeloid leukemia (AML). Patients received atezolizumab 840 mg (days [D] 8 and 22) and guadecitabine 60 mg/m² (D1 and D5) over 28-day cycles. Sixteen patients (median age 73.0 years) enrolled (R/R cohort, n = 11; first-line cohort, n = 5). All patients reported at least 1 AE; 15 patients (93.8%) reported grade ≥ 3 AEs, and 15 patients (93.8%) reported SAEs. Fourteen of the 16 patients (87.5%) died during the trial period due to disease progression (8/14) or AEs (6/14), hence the study was terminated early. One patient (from the R/R AML cohort) achieved a response (CR with incomplete platelet recovery) with a DOR of 27.8 months at study termination. Atezolizumab plus guadecitabine had limited clinical activity in AML and an overall unfavorable benefit-risk profile at the investigated dose levels.

Keywords:

• Oncology
• checkpoint inhibitor
• PD-L1 inhibitor

Acknowledgments

Third-party medical writing assistance, under the direction of Thomas Prebet, was provided by Helen Cathro, Ph.D., of Ashfield MedComms, an Ashfield Health company, and was funded by F. Hoffmann-La Roche Ltd.

Disclosure statement

T.P. has served as a consultant or on advisory boards for AbbVie, Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharma, Takeda, and via Oncology, and has received research funding from Agios, Bristol Myers Squibb, and Jazz Pharma. A.D.G. has served as a consultant or on advisory boards for AbbVie, Aptose, Astellas, Celgene, Daiichi Sankyo, and Genentech, has received research funding from AbbVie, Aptose, Celularity, ADC Therapeutics, Aprea, AROG Pharmaceuticals, Pfizer, and Prelude, and has received honoraria from Dava Oncology. J.G.J. has received research funding (institutional) from AbbVie, AROG Pharmaceuticals, Astellas, Celularity, Daiichi Sankyo, Forma Therapeutics, Forty-Seven, Genentech, Gilead, GlycoMimetics, PTC Therapeutics, and Syros Pharmaceuticals, and has served as a consultant for AbbVie, Actinium Pharmaceuticals, Bristol Myers Squibb, and Novartis. S.K. has served on advisory boards for and received honoraria from Alexion, Astellas Pharma, Daiichi Sankyo, and Omeros Corporation has received speaker’s bureau from Alexion, and is an employee of Janssen. M.R.G. has served as a consultant for AbbVie, Agios, Amgen, Astellas, Blueprint Medicines, Bristol Myers Squibb, Cardinal Health, Daiichi Sankyo, Gilead, Incyte, Karius, Pfizer, Premier, Sierra Oncology, Stemline, and Trovagene, and has received research funding from Incyte and Janssen. M.D., Y.F., C.G., C.L., C.M., and B.C.M. are employees of Genentech, Inc. M.Y. is an employee of F. Hoffmann-La Roche Ltd.

Data availability statement

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Additional information

Funding

This work was supported and funded by F. Hoffmann-La Roche Ltd.